title: Novel ancestral Dysferlin splicing mutation which migrated from the Iberian peninsula to South America.
abstract: Primary dysferlinopathies are a group of recessive heterogeneous muscular dystrophies. The most common clinical presentations are Miyoshi myopathy and LGMD2B. Additional presentations range from isolated hyperCKemia to severe functional disability. Symptomatology begins in the posterior muscle compartment of the calf and its clinical course progresses slowly in Miyoshi myopathy whereas LGMD2B involves predominantly the proximal muscles of the lower limbs. The age of onset ranges from 13 to 60years in Caucasians. We present five patients that carry a novel mutation in the exon12/intron12 boundary: c.1180_1180+7delAGTGCGTG (r.1054_1284del). We provide evidence of a founder effect due to a common ancestral origin of this mutation, detected in heterozygosity in four patients and in homozygosity in one patient.
authors.affiliation: Clinical Unit, Department of Genetics, Faculty of Medicine, University of the Republic, Av. Gral. Flores 2125, Montevideo CP 11800, Uruguay. luvervi@gmail.com
authors.forename: Luis
authors.initials: L
authors.lastname: Vernengo
authors.forename: Jorge
authors.initials: J
authors.lastname: Oliveira
authors.forename: Martin
authors.initials: M
authors.lastname: Krahn
authors.forename: Emilia
authors.initials: E
authors.lastname: Vieira
authors.forename: Rosário
authors.initials: R
authors.lastname: Santos
authors.forename: Luisa
authors.initials: L
authors.lastname: Carrasco
authors.forename: Luís
authors.initials: L
authors.lastname: Negrão
authors.forename: Ana
authors.initials: A
authors.lastname: Panuncio
authors.forename: France
authors.initials: F
authors.lastname: Leturcq
authors.forename: Veronique
authors.initials: V
authors.lastname: Labelle
authors.forename: Elsa
authors.initials: E
authors.lastname: Bronze-da-Rocha
authors.forename: Rosario
authors.initials: R
authors.lastname: Mesa
authors.forename: Carlos
authors.initials: C
authors.lastname: Pizzarossa
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lévy
authors.forename: Maria-Mirta
authors.initials: MM
authors.lastname: Rodriguez
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D000073939:Dysferlin; D004641:Emigration and Immigration; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000473:pathology / Q000648:ultrastructure; D009136:Muscular Dystrophies / Q000208:ethnology* / Q000235:genetics* / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D013020:South America / Q000208:ethnology; D055815:Young Adult
chemical_list: C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins